The main objective of this work is to develop a new technique for delivering antitumor drugs to specified target tissues in order to reduce drug toxicity to normal, nontarget tissues. Our approach involves drug carriers made of phospholipids, called liposomes. The current project has two specific aims: (1) to develop the delivery of antitumor drugs to specific target tissues by using liposomes with different physical and chemical properties, and (2) to define and solve possible problems before use of this drug delivery system for clinical applications. Natural or synthetic phospholipids possess different chemical properties. Liposomes can be prepared with one or more of these lipids to obtain liposomes differing in surface properties. One of the major barriers to using liposomes as carriers of antitumor drugs is their high uptake by organs rich in reticuloendothelial cells (particularly the liver), therefore the search for liposomes with low affinity to the liver is very important. We have found that liposomes prepared with sialic acid or sialogangliosides have a low uptake in the liver, thus making the direction of encapsulated antitumor drugs to other organs more feasible. We have also shown that antitumor drugs encapsulated within liposomes are less toxic to mice than nonencapsulated drugs, but retain their tumoricidal activity. Our investigation of the mechanisms of this reduction in drug toxicity showed that liposome encapsulation provides significant protection to the following cell systems: (1) white blood cells, (2) nucleated cells of the bone marrow, (3) colony-forming stem cells of the spleen and bone marrow, (4) the proliferating intestinal cells, and (5) the antibody producing cells of the spleen.